What is an Adverse Outcome Pathway
In 2012, the OECD launched a new programme on the development of Adverse Outcome Pathways. An Adverse Outcome Pathway (AOP) is an analytical construct that describes a sequential chain of causally linked events at different levels of biological organisation that lead to an adverse health or ecotoxicological effect (see figure). AOPs are the central element of a toxicological knowledge framework being built to support chemical risk assessment based on mechanistic reasoning.
Figure: schematic representation of the Adverse Outcome Pathway (AOP) illustrated with reference to a number of pathways.
The AOP development programme addresses the needs of:
- the OECD Test Guidelines Programme for the identification of new in vitro test methods that are candidates to become OECD Test Guidelines;
- The OECD QSAR Project for the identification of new methods/profilers for grouping chemicals, and;
- the OECD Hazard Assessment activities for the development of Integrated Approaches to Testing and Assessment (IATA), also known as Integrated Testing Strategies, for defined hazard endpoints.
The OECD coordinates its activities with the WHO/IPCS work on Mode of Action, as the AOP concept and the Mode of Action are closely related.
How to make a project proposal
Project proposals for developing an AOP can sent to the OECD Secretariat using the submission of proposals form (word file). Government representatives, academic experts, industry experts, non-governmental organisations, scientific societies, etc. can submit project proposals. The National Coordinators of the Test Guidelines Programme are also available for queries, and should be informed about proposals submitted.
Project proposals are reviewed twice a year and included in the workplan if justified.
A list of projects already in the workplan is available here.
Process for the development of AOP at OECD
This flow diagram (PDF) shows how AOPs are developed, reviewed, agreed and published at OECD. The publication of an AOP descriptive document in the Series on Testing and Assessment does not preclude the publication by authors of the AOP of scientific articles in the peer-reviewed literature; in fact, the working group supports broad distribution of the resulting products.
Most of the AOP development and review is intended to take place via a web-based IT management tool (“AOP Knowledge Base”) which is in development and is being tested until the end of 2013. More information will be made publicly available after the testing phase.
Once developed and reviewed by the Advisory Group on Molecular Screening and Toxicogenomics, and other relevant expert groups under the Test Guidelines Programme, the AOP is endorsed by the Working Group of the National Coordinators of the Test Guidelines Programme and the Task Force on Hazard Assessment, and declassified by the Joint Meeting overseeing the OECD work on chemical safety.
An IT system to develop and evaluate Adverse Outcome Pathways, the AOP Wiki, has been developed for testing by members of the Extended Advisory Group on Molecular Screening and Toxicogenomics and by developers of AOPs included in the work plan. The Wiki provides developers the necessary steps to capture the scientific information in a user-friendly manner. The project is jointly led by the European Commission Joint Research Center and the United States Environmental Protection Agency for the purpose of the OECD programme on the development of AOPs. For more information, please visit the European Commission's Joint Research Center site.